Some vaccines and other medicines contain one or more components called adjuvants which serve to enhance the immunogenicity of the vaccine antigens, thereby making the vaccine more effective. Studies have shown that many aluminum-containing vaccines elicit higher and more prolonged antibody responses than the same vaccines formulated without the adjuvant. There are several types of aluminum-containing salts (“also referred to as alum”) which function as vaccine adjuvants: (i) aluminum phosphate or AlPO4, (ii) aluminum hydroxide or Al(OH)3, and (iii) potassium aluminum sulfate AlK(SO4)2. The effectiveness of each aluminum-containing adjuvant often depends on the characteristics of the specific vaccine and how the manufacturer prepares the vaccine (Baylor et al., “Aluminum salts in vaccines-US perspective,” Vaccine 20:S18-23, 2002). To work as an adjuvant, the antigen typically needs to be adsorbed to the aluminum to keep the antigen at the site of injection.
United States licensed vaccines for children that contain aluminum adjuvants include, without limitation, diphtheria-tetanus-acellular pertussis (DTaP) vaccine, some Haemophilus influenzae type b conjugate (Hib) vaccines, Pneumococcal conjugate vaccine, Hepatitis B vaccines, combination DTaP, Tdap, Hepatitis A vaccines, and Human Papillomavirus vaccine.
PREVNAR®, marketed and sold by Wyeth, is a conjugated pneumococcal vaccine that contains aluminum phosphate as an adjuvant. The antigens in PREVNAR® (conjugated pneumococcal vaccine) are a mixture of polysaccharides from seven different serotypes of Streptococcus pneumoniae bacteria, each conjugated to the carrier protein CRM197. PREVNAR® (conjugated pneumococcal vaccine) is formulated as a clear aqueous liquid containing a colloidal suspension of the antigen—the substance that stimulates the specific protective immune response—adsorbed onto the aluminum adjuvant AlPO4.
While methods of producing aluminum phosphate adjuvant have been described, there remains a need in the art for methods that are more efficient and/or sterile, especially on an industrial scale. In addition, it is desirable that any new method produce aluminum phosphate adjuvant with similar physical, chemical and functional characteristics as the aluminum phosphate adjuvant already in commercial use, e.g., in PREVNAR® (conjugated pneumococcal vaccine).